Sweat chloride and lung function responses to elexacaftor-tezacaftor-ivacaftor in people with cystic fibrosis with two versus one responsive CFTR variants: an analysis of two real-world observational studies.

Background: Among people with cystic fibrosis, sweat chloride and lung function response to elexacaftor-tezacaftor-ivacaftor (ETI) is variable. We hypothesised that the presence of two versus one ETI-responsive CFTR variant could predict response variability.

Methods: In this analysis of two real-world observational studies, data from a French national cohort of adults (aged ≥18 years) with cystic fibrosis and at least one F508del variant treated with ETI and the French compassionate programme for ETI in people (aged ≥6 years) with cystic fibrosis without F508del were used to examine sweat chloride concentrations (SCCs) after ETI initiation, and the absolute change in SCC and percentage of predicted forced expiratory volume in 1 s (ppFEV) following ETI initiation.

Diagnostic significance of intragraft donor-specific anti-HLA antibodies in pulmonary antibody-mediated rejection.

Background: The diagnosis of pulmonary antibody-mediated rejection (AMR) remains challenging with lack of specific defining features. This study evaluated the diagnostic and prognostic significance of intragraft anti human leukocyte antigen (HLA) donor-specific antibodies (gDSA) in pulmonary AMR.

Methods: This multicenter prospective study enrolled adult lung transplant recipients (LTR) with serum anti-HLA DSA (sDSA) >1,000 Luminex mean fluorescence intensity (MFI).

CD146: a promising target in respiratory diseases.

Respiratory diseases are major causes of chronic disorders and death worldwide, involving inflammatory, tumoral or infectious processes. It has been proven that vascular mechanisms are key contributors to the pathogenesis of these diseases. For that purpose, it is essential to describe and validate new biomarkers and/or therapeutic targets responsible for lung vascularisation and/or angiogenesis.

Impaired IgA Mucosal Immunity Following Lung Transplantation: A Potential Trigger for Bronchiolitis Obliterans Syndrome.

Rationale: Bronchiolitis obliterans syndrome (BOS) limits long-term survival after lung transplantation (LuTx) and may be triggered by infections. As immunoglobulin (Ig)A is crucial to ensure adequate mucosal immunity, we explored whether IgA-related mucosal immunity is impaired in BOS.

Methods: Sixty LuTx recipients from the COLT cohort were retrospectively included.

Fatal acute respiratory distress syndrome caused by donor-derived human metapneumovirus after lung transplantation.

Respiratory viral infections, including human metapneumovirus (hMPV), are increasingly recognized as a significant cause of morbidity and mortality in lung transplant recipients (LTRs). We present a case of hMPV pneumonia in a bilateral LTR, likely transmitted by the donor, resulting in severe acute respiratory distress syndrome and leading to death. Next-generation sequencing of hPMV genomes was performed from both the recipient's bronchoalveolar lavage and the organ conservation liquid and strongly supported the presence of donor-derived infection.

Increased delay to lung transplantation for women candidates: gender-based disparity matters in the lung transplant trajectory.

Background: Lung transplantation is a highly dynamic segment of solid organ transplantation in which gender plays a central role. Our objective was to investigate the causes of outcome differences between women and men all along the lung transplantation pathway.

Methods: We used data from the French COhort in Lung Transplantation (COLT) study (12 participating lung transplantation centres).

Forced vital capacity reduction severity in pulmonary fibrosis and post-lung transplantation outcomes.

Background: The ISHLT guidelines recommend early referral to a lung transplantation (LTx) center for patients with interstitial lung disease (ILD) due to the unpredictable course. To our knowledge, no study has assessed the impact of forced vital capacity (FVC) reduction severity on LTx outcomes in ILD. This study aims to determine whether the severity of FVC reduction is associated with post-transplant outcomes in ILD.

Initial therapy in patients with pulmonary arterial hypertension and cardiovascular comorbidities.

Background: European guidelines recommend initial monotherapy in pulmonary arterial hypertension patients with cardiovascular comorbidities based on the limited evidence for combination therapy in this growing population.

Methods: A retrospective analysis was conducted on incident pulmonary arterial hypertension patients enrolled in the French Pulmonary Hypertension Registry between 2009 and 2020. Propensity score matching was used to investigate initial dual oral combination therapy oral monotherapy in patients with at least one cardiovascular comorbidity ( hypertension, obesity, diabetes and coronary artery disease).

Characteristics and outcomes of patients with LAM receiving sirolimus in France based on real-life data.

LAM is a rare multi-cystic lung disease for which treatment with sirolimus is indicated in cases of moderate or severe lung disease or declining lung function. The aim of this study was to describe patients treated with sirolimus for LAM and their outcomes. This retrospective observational study was based on data from the French national health insurance data system (SNDS).

Pulmonary fibrosis in patients with autoimmune pulmonary alveolar proteinosis: a retrospective nationwide cohort study.

Background: Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease that may progress towards pulmonary fibrosis. Data about fibrosis prevalence and risk factors are lacking.

Methods: In this retrospective multicentre nationwide cohort, we included patients newly diagnosed with aPAP between 2008 and 2018 in France and Belgium.

Usefulness of monitoring mycophenolic acid exposure in systemic sclerosis-related interstitial lung disease: a retrospective cohort study.

Background: Systemic sclerosis-related interstitial lung disease (SSc-ILD) represents a significant cause of morbidity and mortality in Systemic Sclerosis (SSc). Mycophenolate mofetil (MMF) is currently the first line treatment for SSc-ILD. There is no recommendation on the dosage of mycophenolic acid (MPA) blood concentrations, so we aimed to study the correlation between MPA exposure and respiratory outcomes in this population.

Circulating Vesicular-bound HLA-G as Noninvasive Predictive Biomarker of CLAD After Lung Transplantation.

Background: Circulating extracellular vesicles (EVs) have shown promising results as noninvasive biomarkers for predicting disease outcomes in solid organ transplantation. Because in situ graft cell expression of the tolerogenic molecule HLA-G is associated with acceptance after lung transplantation (LTx), we hypothesized that plasma EV-bound HLA-G (HLA-G EV ) levels could predict chronic lung allograft dysfunction (CLAD) development.

Methods: We analyzed 78 LTx recipients from the Cohort-for-Lung-Transplantation cohort, all in a stable (STA) state within the first year post-LTx.

The expanded French compassionate programme for elexacaftor-tezacaftor-ivacaftor use in people with cystic fibrosis without a F508del CFTR variant: a real-world study.

Background: Elexacaftor-tezacaftor-ivacaftor has been approved in Europe for people with cystic fibrosis with at least one F508del CFTR variant. Additionally, it is approved by the US Food and Drug Administration (FDA) for people with cystic fibrosis with at least one of 177 rare variants. The aims of this study were to describe the clinical response to elexacaftor-tezacaftor-ivacaftor for people with cystic fibrosis without a F508del CFTR variant in France and to determine CFTR variant responsiveness to elexacaftor-tezacaftor-ivacaftor based on the observed clinical response.

Management of immunosuppression in lung transplant recipients and COVID-19 outcomes: an observational retrospective cohort-study.

Background: The aim of this study was to assess the impact of immunosuppression management on coronavirus disease 2019 (COVID-19) outcomes.

Methods: We performed a single-center retrospective study in a cohort of 358 lung transplant recipients (LTx) over the period from March 2020 to April 2022. All included symptomatic patients had at least one positive SARS-CoV-2 rt-PCR.

Phenotypes and outcome of diffuse pulmonary non-amyloid light chain deposition disease.

Background: Light chain deposition disease (LCDD) is a very rare entity. Clinical manifestations of LCDD vary according to the organs involved. Data on pulmonary LCDD are scarce and limited to small series or case reports.

Multisystemic Effects of Elexacaftor-Tezacaftor-Ivacaftor in Adults with Cystic Fibrosis and Advanced Lung Disease.

Limited data exist on the safety and effectiveness of elexacaftor-tezacaftor-ivacaftor (ETI) in people with cystic fibrosis (pwCF) and advanced lung disease. To evaluate the effects of ETI in an unselected population of pwCF and advanced lung disease. A prospective observational study, including all adults aged 18 years and older with percentage predicted forced expiratory volume in 1 second (ppFEV) ⩽ 40 who initiated ETI from December 2019 to June 2021 in France, was conducted.

High risk of lung cancer in surfactant-related gene variant carriers.

Background: Several rare surfactant-related gene (SRG) variants associated with interstitial lung disease are suspected to be associated with lung cancer, but data are missing. We aimed to study the epidemiology and phenotype of lung cancer in an international cohort of SRG variant carriers.

Methods: We conducted a cross-sectional study of all adults with SRG variants in the OrphaLung network and compared lung cancer risk with telomere-related gene (TRG) variant carriers.

Evaluation of computed tomography in the diagnosis of ultrasound-proven diaphragm dysfunction.

Introduction: Computed tomography (CT) is routinely employed on the evaluation of dyspnea, yet limited data exist on its assessment of diaphragmatic muscle. This study aimed to determine the capability of CT in identifying structural changes in the diaphragm among patients with ultrasound-confirmed diaphragmatic dysfunction.

Methods: Diaphragmatic ultrasounds conducted between 2018 and 2021 at our center in Marseille, France, were retrospectively collected.

Similarities and differences of interstitial lung disease associated with pathogenic variants in SFTPC and ABCA3 in adults.

Background And Objective: Variants in surfactant genes SFTPC or ABCA3 are responsible for interstitial lung disease (ILD) in children and adults, with few studies in adults.

Methods: We conducted a multicentre retrospective study of all consecutive adult patients diagnosed with ILD associated with variants in SFTPC or ABCA3 in the French rare pulmonary diseases network, OrphaLung. Variants and chest computed tomography (CT) features were centrally reviewed.